| Title: |
Spatial Transcriptomics Resolve an Emphysema-Specific Lymphoid Follicle B Cell Signature in Chronic Obstructive Pulmonary Disease |
| Authors: |
Rojas-Quintero, Joselyn; Ochsner, Scott A.; New, Felicia; Divakar, Prajan; Yang, Chen Xi; Wu, Tianshi David; Robinson, Jerid; Chandrashekar, Darshan Shimoga; Banovich, Nicholas E.; Rosas, Ivan O.; Sauler, Maor; Kheradmand, Farrah; Gaggar, Amit; Margaroli, Camilla; San Jose Estepar, Raul; McKenna, Neil J.; Polverino, Francesca |
| Contributors: |
Baylor College of Medicine; National Heart, Lung, and Blood Institute |
| Source: |
American Journal of Respiratory and Critical Care Medicine ; volume 209, issue 1, page 48-58 ; ISSN 1073-449X 1535-4970 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2024 |
| Description: |
Rationale Within chronic obstructive pulmonary disease (COPD), emphysema is characterized by a significant yet partially understood B cell immune component. Objectives To characterize the transcriptomic signatures from lymphoid follicles (LFs) in ever-smokers without COPD and patients with COPD with varying degrees of emphysema. Methods Lung sections from 40 patients with COPD and ever-smokers were used for LF proteomic and transcriptomic spatial profiling. Formalin- and O.C.T.-fixed lung samples obtained from biopsies or lung explants were assessed for LF presence. Emphysema measurements were obtained from clinical chest computed tomographic scans. High-confidence transcriptional target intersection analyses were conducted to resolve emphysema-induced transcriptional networks. Measurements and Main Results Overall, 115 LFs from ever-smokers and Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1–2 and GOLD 3–4 patients were analyzed. No LFs were found in never-smokers. Differential gene expression analysis revealed significantly increased expression of LF assembly and B cell marker genes in subjects with severe emphysema. High-confidence transcriptional analysis revealed activation of an abnormal B cell activity signature in LFs (q-value = 2.56E-111). LFs from patients with GOLD 1–2 COPD with emphysema showed significantly increased expression of genes associated with antigen presentation, inflammation, and B cell activation and proliferation. LFs from patients with GOLD 1–2 COPD without emphysema showed an antiinflammatory profile. The extent of centrilobular emphysema was significantly associated with genes involved in B cell maturation and antibody production. Protein-RNA network analysis showed that LFs in emphysema have a unique signature skewed toward chronic B cell activation. Conclusions An off-targeted B cell activation within LFs is associated with autoimmune-mediated emphysema pathogenesis. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1164/rccm.202303-0507le |
| Availability: |
https://doi.org/10.1164/rccm.202303-0507le; https://academic.oup.com/ajrccm/article-pdf/209/1/48/66431554/ajrccm_209_1_48.pdf |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.5AA5A8D4 |
| Database: |
BASE |